17 research outputs found
Recruitment and selection strategies in optometric education towards addressing human resource disparities in sub-Saharan Africa
Mutations in Zebrafish lrp2 Result in Adult-Onset Ocular Pathogenesis That Models Myopia and Other Risk Factors for Glaucoma
The glaucomas comprise a genetically complex group of retinal neuropathies that typically occur late in life and are characterized by progressive pathology of the optic nerve head and degeneration of retinal ganglion cells. In addition to age and family history, other significant risk factors for glaucoma include elevated intraocular pressure (IOP) and myopia. The complexity of glaucoma has made it difficult to model in animals, but also challenging to identify responsible genes. We have used zebrafish to identify a genetically complex, recessive mutant that shows risk factors for glaucoma including adult onset severe myopia, elevated IOP, and progressive retinal ganglion cell pathology. Positional cloning and analysis of a non-complementing allele indicated that non-sense mutations in low density lipoprotein receptor-related protein 2 (lrp2) underlie the mutant phenotype. Lrp2, previously named Megalin, functions as an endocytic receptor for a wide-variety of bioactive molecules including Sonic hedgehog, Bone morphogenic protein 4, retinol-binding protein, vitamin D-binding protein, and apolipoprotein E, among others. Detailed phenotype analyses indicated that as lrp2 mutant fish age, many individuals—but not all—develop high IOP and severe myopia with obviously enlarged eye globes. This results in retinal stretch and prolonged stress to retinal ganglion cells, which ultimately show signs of pathogenesis. Our studies implicate altered Lrp2-mediated homeostasis as important for myopia and other risk factors for glaucoma in humans and establish a new genetic model for further study of phenotypes associated with this disease
Zebrafish as a model for kidney function and disease
Kidney disease is a global problem with around three million people diagnosed in the UK alone and the incidence is rising. Research is critical to develop better treatments. Animal models can help to better understand the pathophysiology behind the various kidney diseases and to screen for therapeutic compounds, but the use especially of mammalian models should be minimised in the interest of animal welfare. Zebrafish are increasingly used, as they are genetically tractable and have a basic renal anatomy comparable to mammalian kidneys with glomerular filtration and tubular filtration processing. Here, we discuss how zebrafish have advanced the study of nephrology and the mechanisms underlying kidney disease
Individual, social, and environmental factors affecting salivary and fecal cortisol levels in captive pied tamarins (Saguinus bicolor)
This is the peer reviewed version of the following article: Price, E., Coleman, R., Ahsmann, J., Glendewar, G., Hunt, J., Smith, T. & Wormell, D. (2019). Individual, social, and environmental factors affecting salivary and fecal cortisol levels in captive pied tamarins (Saguinus bicolor). American Journal of Primatology, 81(8), which has been published in final form at https://doi.org/10.1002/ajp.23033. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingPied tamarins (Saguinus bicolor) are endangered New World primates, and in captivity
appear to be very susceptible to stress. We measured cortisol in 214 saliva samples
from 36 tamarins and in 227 fecal samples from 27 tamarins, and investigated
the effects of age, sex, pregnancy, rearing history, social status, weight, group
composition, and enclosure type using generalized linear mixed models. There was no
effect of age on either fecal or salivary cortisol levels. Female pied tamarins in late
pregnancy had higher fecal cortisol levels than those in early pregnancy, or
nonpregnant females, but there was no effect of pregnancy on salivary cortisol.
Females had higher salivary cortisol levels than males, but there was no effect of
rearing history. However, for fecal cortisol, there was an interaction between sex and
rearing history. Hand‐reared tamarins overall had higher fecal cortisol levels, but
while male parent‐reared tamarins had higher levels than females who were parent‐
reared, the reverse was true for hand‐reared individuals. There was a trend towards
lower fecal cortisol levels in subordinate individuals, but no effect of status on
salivary cortisol. Fecal but not salivary cortisol levels declined with increasing weight.
We found little effect of group composition on cortisol levels in either saliva or feces,
suggesting that as long as tamarins are housed socially, the nature of the group is of
less importance. However, animals in off‐show enclosures had higher salivary and
fecal cortisol levels than individuals housed on‐show. We suggest that large on‐show
enclosures with permanent access to off‐exhibit areas may compensate for the
effects of visitor disturbance, and a larger number of tamarins of the same species
housed close together may explain the higher cortisol levels found in tamarins living
in off‐show accommodation, but further research is needed
FYVE1 is essential for vacuole biogenesis and intracellular trafficking in Arabidopsis
The plant vacuole is a central organelle that is involved in various biological processes throughout the plant life cycle. Elucidating the mechanism of vacuole biogenesis and maintenance is thus the basis for our understanding of these processes. Proper formation of the vacuole has been shown to depend on the intracellular membrane trafficking pathway. Although several mutants with altered vacuole morphology have been characterized in the past, the molecular basis for plant vacuole biogenesis has yet to be fully elucidated. With the aim to identify key factors that are essential for vacuole biogenesis, we performed a forward genetics screen in Arabidopsis (Arabidopsis thaliana) and isolated mutants with altered vacuole morphology. The vacuolar fusion defective1 (vfd1) mutant shows seedling lethality and defects in central vacuole formation. VFD1 encodes a Fab1, YOTB, Vac1, and EEA1 (FYVE) domain-containing protein, FYVE1, that has been implicated in intracellular trafficking. FYVE1 localizes on late endosomes and interacts with Src homology-3 domain-containing proteins. Mutants of FYVE1 are defective in ubiquitin-mediated protein degradation, vacuolar transport, and autophagy. Altogether, our results show that FYVE1 is essential for plant growth and development and place FYVE1 as a key regulator of intracellular trafficking and vacuole biogenesis